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Instability of prefrontal signal processing in schizophrenia
Georg Winterer1, Francesco Musso, Christian Beckmann
1Genes, Cognition and Psychosis Program, NIH, NIMH, 10 Center Dr., MSC 1379, Bethesda, MD 20892, USA.
The American Journal of Psychiatry
|November 1, 2006
Summary
Schizophrenia involves unstable brain signal processing, particularly in the prefrontal cortex. This instability, measured by increased noise variance, correlates with symptoms and abnormal brain activation patterns in patients.
Area of Science:
- Neuroscience
- Psychiatry
- Cognitive Science
Background:
- Prefrontal cortex dysfunction is a hallmark of schizophrenia.
- Electrophysiological studies suggest unstable signal processing in prefrontal cortical microcircuits due to reduced phase-synchronization, leading to increased stimulus-related variability or "noise".
Purpose of the Study:
- To investigate signal stability in the prefrontal cortex of patients with schizophrenia using functional magnetic resonance imaging (fMRI).
- To examine the relationship between signal stability and traditional measures of brain activation.
- To explore the correlation between signal instability and psychotic symptoms.
Main Methods:
- fMRI was used during a visual two-choice reaction task in 12 patients with schizophrenia and 16 healthy comparison subjects.
- Event-related blood-oxygen-level-dependent (BOLD) responses were analyzed for residual noise variance.
- Independent component analysis (ICA) was applied to the medial prefrontal cortex.
Main Results:
- Patients with schizophrenia exhibited increased residual noise variance in their BOLD responses, which predicted prefrontal activation levels.
- Higher residual noise variance in the left hemisphere correlated significantly with the severity of psychotic symptoms.
- ICA revealed a "fractionized" and unfocused pattern of brain activation in patients with schizophrenia.
Conclusions:
- Unstable cortical signal processing is implicated in the abnormal prefrontal activation patterns observed in schizophrenia.
- This signal instability may be a key neural mechanism underlying psychosis in schizophrenia.
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